Stabilized aqueous solutions of paraminosalicylic acid salts



.EAI'ENT ()FFICE STABILIZED AQUEOUS SOLUTIONS OF PARA- AMINOSALICYLIC ACID SALTS Roger G. Douris, Paris, and Jacques M. Bory, Montmoreney, France UNITED STAT No Drawing. Application December 8, 1950, Serial No. 199,926

Claims priority, application France March 25, 1950 2 Claims. (01. 167-58) 1 2 The salts of paraaminosalicylic acid in aquethat it may be desirable to incorporate sodium cus solution are known to be very susceptible bicarbonate in a small proportion, say 0.1 to to oxidation. As an example, when it is at- 0.6 per cent by weight according to the content tempted to sterilize an aqueous solution of sodium of paraaminosalicylic acid salt in the aqueous salt of paraaminosalicylic acid as is employed 5 solution stabilized according to our invention, for therapeutic purposes, the initially clear, at any stage of or after the production of said colourless solution assumes a brown hue and besolution, but before the sterilization thereof.

comes toxic. ExampZe.-Qne gram of sodium formaldehyde- It is an object of our invention to provide a sulfoxylate was dissolved in a litre of water and process for stabilising aqueous solutions of then 30 grams of sodium salt of paraaminoalkaline and alkali-earth metal salts of parasalicylic acid were added thereto.

aminosalicylic acid, more particularly aqueous The solution thus produced was put in ampullae solutions of the sodium salt, whereby the soluwhich were sterilized for half an hour at temtions can safely be sterilized and kept without peratures from 100 to 120 C. The solution kept noticeable alteration. very well, remained clear and colourless, and tests Another object is to provide new aqueous solushowed it was not toxic.

tions of alkaline and alkali-earth metal salts of The same results were observed with a like paraaminosalicylic acid, more particularly aquesolution subjected to tyndallization.

ous solutions of the sodium salt, which are stable It was found that the amounts of sodium and capable of being sterilized or tyndallized 2o formaldehyde-sulioxylate required for stabilizwithout noticeable alteration and can be reliably ing aqueous solutions containing from 5 to 200 employed for intravenous injection for therapeugrams of sodium salt of paraaminosalicylic acid tic purposes without toxic effects. ranged from 0.1 to grams.

We have found that a certain reducing sub- Aqueous solutions of calcium salt of parastance when added to aqueous solutions of 5 aminosalicylic acid could likewise be stabilized.

alkaline and alkali-earth metal salts of para- In every case it was found that decarboxylaaminosalicylic acid is capable of stabilizing the tion of the paraaminosalicylic acid salt is lessened Same and p ting such alterations as colourawhen sodium bicarbonate has been incorporated tion and toxic effects which are ascribable not in th solution, only to oxidation but also presumably to other What we claim is; chemical reactions such as condensations.

1. A heat sterilizable aqueous solution for in- This reducing substance is sodium formaldetravenous injection, which contains 0:5 to 20 per hyde-sulfoxylate which is desirable because it can cent by weight of sodium salt of paraaminobe y d in proportions which in addition to salicylic acid together with 0.01 to 1 per cent by being effective are not objectionable for theraweight of sodium formaldehyde-sulfoxylate.

peutic administration.

2. The composition of claim 1, further contain- The aqueous solutions to be stabilized may 0011- ing.0.1 to 0.6 per cent by weight of added sodium tain from 0.5 to 20 per cent by weight of parabicarbonate. aminosalicylic acid salts. ROGER G. DOURIS.

As to the proportion of the reducing substance JACQUES M. BORY.

4 this may vary over a wide range there being in principle no upper limit for such proportion, but References Cited In the file of 171115 patent for practical purposes a proportion of about 0.01 UNITED STATES PATENTS to 1 per cent reckoned on the weight of the aque- Number N ame Date ggg jg to be Stabmzed 18 generally Sans 2,540,785 Hultquist Feb. 6 1951 It is preferable to add the reducing substance H R REFERENCES to water and then to dissolve the required amount The Lancet, Volume 254, January 31, 1948 page of paraaminosalicylic acid salt into the solution thus produced to produce a stabilized solution according to this invention. September 9, 1949.

Oberweger: The Pharm. Journal, page 36,

With a view to reducing decarboxylation of the Hicks: American Journal Ophthalmology, 1937,

paraaminosalicylic acid salt, we have also found pages 1040 to 1041. 

1. A HEAT STERILIZER AQUEOUS SOLUTION FOR INTRAVENOUS INJECTION, WHICH CONTAINS 0.5 TO 20 PER CENT BY WEIGHT OF SODIUM SALT OF PARAAMINOSALICYLIC ACID TOGETHER WITH 0.01 TO 1 PER CENT BY WEIGHT OF SODIUM FORMALDEHYDE-SULFOXYLATE. 